Successful treatment of verruca vulgaris with Thuja occidentalis in a renal allograft recipient

Introduction

Human Papillomavirus (HPV) driven verruca vulgaris (warts) increases the risk of squamous cell carcinoma (SCC) in solid organ transplant recipients, with a reported incidence of 24% to 100%.[1] The incidence increases with the duration of transplant. The available treatment modalities have limited response. Thuja occidentalis is used to treat warts in homeopathic system of medicine.

Case Report

A 34-year-old male, a clerk by profession underwent a living donor renal transplantation in 2006 and was maintained on cyclosporine (150 mg daily), prednisolone (10 mg daily), and mycophenolate mofetil (1500 mg daily). He did not receive lytic induction. He was anti-HCV positive and received a 6-months course of interferon alpha 2b before transplantation. During early post-transplant period, he had acute cellular rejection Banff type II A, requiring three doses of methyl prednisolone. There were no opportunistic infections or reactivation of HCV during the 1^st year of follow-up.

A year after transplantation, he developed multiple warty lesions on the dorsum of the fingers of both hands suggestive of verruca vulgaris. These lesions were treated with cryotherapy, cauterization, and radiosurgery with marginal improvement. However, 4 months later, the distal end of the right middle finger revealed ischemic changes and necrosis, needing amputation of distal two phalanges [Figure 1a]. Histology of the amputated finger showed nests of malignant squamous cells with keratin pearls infiltrating the dermis [Figure 1b]. He returned to our center where excisional biopsies of few existing warts were done. Histology showed hyperkeratosis, parakeratosis, acanthosis and prominent giant eosinophilic keratohyalin granules and eosinophilic intranuclear inclusions with viral cytopathic effect, and mild dysplasia consistent with verruca vulgaris [Figure 1c]. Human papillomavirus (HPV) genotype Ia was identified from the specimen. Having lost part of the finger on the right hand, the patient had crippling anxiety and fear that the remaining warts would claim his other fingers and his livelihood. Cyclosporine was replaced with everolimus. Ketoconazole augmentation was given for cost reduction. Cryotherapy and cauterization failed over the next 6 months. At this time, the patient was treated with Thuja occidentalis (T. occidentalis) extract, orally and topically for a period of 7 days at his native place. For external applications, he received mother tincture and as oral preparation he was given potentized medium (power 1^m= 1000 times) T. occidentalis as 2 globules thrice a day. By the end of 3^rd week of therapy, the warts dropped off leaving only small superficial scars [Figure 1d]. The allograft function remained unaffected at creatinine of 1.5 mg/dl. He has been followed up for one year and has not had any recurrence.

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Figure 1

(a) Amputated right middle finger with multiple warts. (b) Squamous cell carcinoma of skin of same finger (H and E, ×200). (c) Skin lesion with prominent giant eosinophilic keratohyalin granules and eosinophilic intranuclear inclusions (H and E, ×200). (d) Disappearance of lesions after thuja treatment

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Discussion

Globally, approximately 15% of all malignant tumors are caused by viruses. Early rejections, multiple viral infections, cyclosporine therapy, exposure to ultra voilet (UV) light predispose to warts. Though proliferation signal inhibitors are known to reduce the incidence of non-melanoma skin cancers, there is no evidence of eradicating papilloma viruses.[2] Our patient was HCV positive and was exposed to higher immunosuppression due to early post-transplant rejection.

The available modalities of treatment for warts include cryotherapy, intralesional bleomycin and interferon, topical 5-fluorouracil and dinitrochlorobenzene, photodynamic therapy, and pulsed dye laser have not shown to be of benefit in randomized controlled trial.[3] Other treatments include topical imiquimod, curettage and excision, glutaraldehyde, formaldehyde, podophyllin, podophyllotoxin, and cantharidin. However, none of them are supported by randomized controlled trials.

T. occidentalis, an extract from white cedar (Arbor vitae or the white oak) is indigenous to eastern North America and grown in Europe as an ornamental tree. In folk medicine, extract from dried twig tips has been used to treat bronchial catarrh, enuresis, cystitis, psoriasis, uterine carcinomas, amenorrhea, and rheumatism. Hansel et al., have described the drug to contain 1.4-4% essential oil (critical factor as medicinal herb), 60% of which is thujone, which corresponds to 2.4% thujone in the whole drug.[4] The pharmacological potential of T. occidentalis has been investigated in various in vitro and in vivo studies. It showed significant increase in interleukin 1, interleukin 6, and tumour necrosis factor alpha and caused local activation of cytokine producing cells for priming without a systemic rise.[5] Antibody-producing lymphocytes increased in the hemolytic plaque assay in vitro.[6] Thuja causes T-cell induction particularly of Cluster Differentiation 4 (CD 4) positive T-helper cells in connection with an increased production of Interleukin 2.[7] Thus, thuja has shown definite anti-human immunodeficiency virus-1 activity. A 2-year prospective clinical and therapeutic experience of patients with HPV infection diagnosed based on cytology and or biopsy, which had recurred after treatment found that thuja helped to eradicate the papillomatous lesions.[8] Hexane, chloroform, and ethyl acetate fractions of thuja were tried of which the chloroform fraction rated superior with complete eradication in all the patients in a randomized control study.[9]

In summary, we report a case of verruca vulgaris leading to cutaneous squamous cell carcinoma in a young renal allograft recipient, where treatment with T. occidentalis helped to eradicate the remaining lesions without compromising graft function.